Injection Of Desipramine Research Articles

Further evidence for a physiological role for hypothalamic dopamine in thermoregulation in the rat.

1. Intrahypothalamic injection of either dopamine or noradrenaline in a dose volume of 1 mul. caused a fall in core temperature in lightly restrained rats maintained at an ambient temperature of 17 +/- 1 degrees C.2. The hypothermic effects of dopamine (10 mug) and noradrenaline (2 mug) were selectively antagonized by systemic pre-treatment with pimozide (0.5 mg/kg) and phentolamine (1 mg/kg) respectively.3. The location of the dopamine- and noradrenaline-sensitive sites were defined more accurately by reducing the dose volume to 0.5 mul. and making injections at different points throughout the preoptic region.4. Both the dopamine- and the noradrenaline-sensitive sites were located within the preoptic region, but they did not have identical locations being separated by a distance of 0.4 mm.5. Unilateral intrahypothalamic injection of 6-hydroxydopamine (10 mug in 2 mul.) caused a significant fall in core temperature, which was antagonized by systemic injection of either pimozide or phentolamine.6. Rats placed 0.65 m below a 250 W infra-red lamp responded to the imposed heat load by vasodilation of tail skin blood vessels, indicated by an increased tail skin temperature.7. Rats were tested two weeks after bilateral intrahypothalamic injection of 6-hydroxydopamine (10 mug in 2 mul.). This pre-treatment significantly reduced the increase in tail skin temperature so that the rats were less able to withstand the imposed heat load. Rats receiving similar 6-hydroxydopamine pre-treatment following injection of desipramine (25 mg/kg, I.P.) were also less able to cope with a heat load.8. Three serial sections (0.8 mm thick) were prepared from the preoptic area of the rat brain, one anterior, one posterior and one corresponding to the dopamine-sensitive site.9. Pre-treatment with 6-hydroxydopamine reduced both the dopamine and the noradrenaline concentration in the dopamine-sensitive site. Pre-treatment with desipramine and 6-hydroxydopamine selectively reduced dopamine.10. These results indicate that there are receptors for both dopamine and noradrenaline in the preoptic anterior hypothalamus, which mediate a fall in core temperature in rats, but the evidence suggests that it is endogenous dopamine which is more likely to play an important physiological role.

Effects of chronic desipramine treatment on rat brain noradrenergic responses to α-adrenergic drugs

It has been previously reported that long-term tricyclic antidepressant treatment in the rat causes a subsensitivity of central β-receptor-stimulated adenylate cyclase along with alterations of brain norepinephrine (NE) content and metabolism. We have confirmed earlier findings that after one week of desipramine treatment (5.0 mg/kg b.i.d.) brain NE levels decline while NE metabolism is similar to control animals, but is above control after 12 days of treatment. Single cell recordings from noradrenergic neurons of the locus coeruleus (LC) show that after one week of desipramine treatment, neuronal firing rate is lower than in control rats but greater than that seen in response to acutely administered drug. Furthermore, desipramine injection in a dose which profoundly altered LC impulse flow in control rats produced little or no effect on impulse flow in chronically treated rats. Of 25 or 250 μg/kg doses of clonidine, which are equieffective for decreasing brain NE metabolism in control animals, only the larger dose decreased NE metabolism in 12 day desipramine-treated rats. The postsynaptic α-antagonist prazosin (5.0 mg/kg) increased NE metabolism in both groups. These results suggest that presynaptic ( α 2) adrenoreceptors become subsensitive during long-term desipramine treatment, thus allowing recovery of noradrenergic impulse flow in the presence of NE uptake inhibition.

Effect of thyrotropin-releasing hormone (TRH) and antidepressant agents on brain stem and hypothalamic multiple unit activity in the cat

The EEG and MUA (multiple unit activity) of mesencephalic reticular formation (MRF), area hypothalami posterior (PH), and area hypothalami anterior (AH) were studied in chronically implanted freely moving cats. The effects of thyrotropin-releasing hormone (TRH) and some antidepressant agents were tested on neuronal activity. Desipramine and imipramine resulted in a dose-dependent decline of MUA of all structures with the most significant decrease of activity in PH. A single injection of TRH resulted in slight or moderate gross behavioral changes and vegetative excitation lasting for 30-50 min with variable MUA levels. In the course of repetitive TRH treatment on consecutive days the gross behavioral changes and the vegetative symptoms failed to develop by the 3rd or 4th day. By that time the MUA changes of PH and MRF showed similar characteristics in response to TRH administration which was observed following the injection of desipramine and imipramine. The drugs, except for TRH, induced a suppression of paradoxical sleep cycles.

Stressor-induced release of substances from the rat amygdala detected by the push-pull cannula.

THE push-pull cannula, originally used to determine the release of endogenous acetylcholine1, has been combined with intraventricular injection of radioactively labelled noradrenaline2 and other substances to investigate the release of noradrenaline and its metabolites after electrical brain stimulation in the free-moving rat3. The technique has also been used to study the release of noradrenaline, serotonin, urea, inulin and α-aminoisobutyric acid from the olfactory bulb after olfactory stimulation in anaesthetized rats4 and the release of noradrenaline, its metabolites and urea after injections of desipramine and reserpine5. Although noradrenaline has been detected in all cases, simultaneous release of such substances as inulin and urea4 has raised questions about the meaning and specificity of the release of noradrenaline.